The formation of adhesions is a frequent and unfortunate result of many surgeries. Adhesions are fibrous bands connecting tissue surfaces that are normally separated. Adhesions are particularly common following abdominal and pelvic surgeries such as hernia repair, gynaecological surgeries and colorectal surgeries.
Trauma to the tissue caused by handling and drying during surgery causes a fibrinous exudate to be released. If the exudate is not absorbed or lysed, it may collect in the peritoneal or pelvic cavity where it is converted into an adhesion. The exudate becomes ingrown with fibroblasts, collagen is deposited and blood vessels begin to form, allowing organisation of the adhesion.
The formation of adhesions can lead to serious complications such as small bowel obstruction, female infertility and chronic pain. Patients may need to undergo further surgery to dissect adhesions, with no guarantees that new adhesions will not form.
Techniques to reduce adhesion formation include lavage of the peritoneal cavity, administration of pharmacological agents and mechanical separation of the tissues. Post-operative hemostasis, the physiologic process whereby bleeding is halted, can also decrease the risk of adhesion formation, as well as conferring other benefits.
Unfortunately, current procedures for reducing adhesions and/or achieving hemostasis are not particularly effective and can be unpleasant for the patient. In addition, in some circumstances treatments aimed at hemostasis may increase the risk of adhesion formation.
For example, following endoscopic sinus surgery (ESS) used to treat chronic sinusitis, patients must endure uncomfortable nasal packing to control bleeding. However, removal of the nasal packs can cause mucosal trauma which increases the likelihood that adhesions will form. Studies have shown that even dressings incorporating known topical hemostatic agents such as thrombin, fibrin, fibrinogen and collagen can cause a significant increase in the formation of adhesions (see for example, Chandra R. K., Kern R. C., Advantages and disadvantages of topical packing in endoscopic sinus surgery, Curr Opin Otolaryngol Head Neck Surg 2004, 12, 21-26). Adhesion formation requiring further surgery occurs in 10-30% of patients undergoing ESS.
Polymer solutions and gels have been applied to target areas to reduce adhesions. For example, gels have been used to coat surgically exposed tissues before closing the surgical site. Some approaches allow for the polymers to be added to the patient in situ, in a solution and then chemically reacted to form covalent cross-links so as to create a polymer network. For example, SprayGel™ is a PEG-based material that forms an adhesion barrier when applied to tissue.
Polysaccharide polymers such as chitosan are also well known as gel forming medicinal agents. Chitosan is recognised to have wound healing properties. For example, U.S. Pat. No. 5,836,970 discloses chitosan and alginate wound dressings that may be prepared as fibers, powders, films, foams, or water-swellable hydrocolloids. U.S. Pat. No. 5,599,916 discloses a water-swellable, water-insoluble chitosan salt that can be used in wound dressings, and U.S. Pat. No. 6,444,797 discloses a chitosan microflake that can be used as a wound dressing or skin coating.
Chitosan has also been shown to have a preventative effect on peritoneal adhesion in rats (Preventive effects of chitosan on peritoneal adhesion in rats, Zhang, Zhi-Liang et al., World J Gastroenterol, 2006, 12(28) 4572-4577.
Derivatives of chitosan have also been investigated for their effects on wound-healing and adhesion prevention. For example, PCT publication WO 96/35433 describes the use of N,O-carboxymethylchitosan for the prevention of surgical adhesions. N,O-carboxymethylchitosan has also been discussed in:                (i) Kennedy, R. et al., Prevention of experimental postoperative adhesions by N,O-carboxymethyl chitosan, Surgery, 1996, 120, 866-70;        (ii) Costain, D. J. et al., Prevention of postsurgical adhesions with N,O-carboxymethylchitosan: Examination of the most efficacious preparation and the effect of N,O-carboxymethyl chitosan on postsurgical healing, Surgery, 1997; 121, 314-9;        (iii) Krause, T. J. et al., Prevention of pericardial adhesions with N,O-arboxymethylchitosan in the Rat Model, Journal of Investigative Surgery, 2001, 14, 93-97;        (iv) Diamond, Michael P. et al., Reduction of postoperative adhesions by N,O-arboxymethylchitosan: a pilot study, Fertil Steril 2003, 80, 631-636;        (v) Diamond, Michael P. et al., Reduction of post operative adhesions by N,O-carboxymethylchitosan: A Pilot Study, The Journal of the American Association of Gynecologic Laparoscopists, 2004, 11(1), 127; and        (vi) Lee, Timothy D. G. et al., Reduction in postoperative adhesion formation and re-formation after an abdominal operation with the use of N,O-carboxymethyl chitosan, Surgery, 2004, 135, 307-312.        
PCT publication WO 98/22114 discusses the use of chitosan combined with sulphated mono-, di-, or oligo-saccharides for enhancing wound healing in collagen-containing tissues. PCT publication WO 96/02260 describes chitosan in combination with heparin, heparin sulphate or dextran sulphate. This combination is said to promote healing of dermal wounds.
PCT publication WO 04/006961 describes a gel for immobilizing and encapsulating cells formed by cross-linking neutral chitosan with a bifunctional multifunctional aldehyde or aldehyde-treated hydroxyl-containing polymer.
Despite these efforts, adhesion formation still commonly occurs in many areas of surgery. Therefore, there is still a need a great need for new polymeric materials with medical efficacy for hemostasis and adhesion prevention that can be used to improve surgical outcomes.
Accordingly, it is an object of the invention to provide a hydrogel that can be applied to a wound to assist wound healing, or to provide the public with a useful choice.